Thrombolytic agents including plasminogen activators and heparin compounds have been employed to dissolve blood clots or thrombi in native blood vessels and in vascular grafts and dialysis grafts. Such plasminogen activators include streptokinase, urokinase and tissue plasminogen activator (t-PA) and their analogues have been administered as lytic agents for lysis of arterial and venous thromboses.
A discussion of the prior art thrombectomy methods and apparatus for medically treating and removing a thrombus or blood clot in a blood vessel is set forth in U.S. Pat. No. 5,370,653 to Cragg, incorporated herein by reference, which discloses a thrombolytic brush method and apparatus for performing a thrombectomy. Attention is also directed to the article by A. H. Cragg M. D., entitled "New Developments in Thrombolytic Therapy" in Ninth Annual International Symposium on Vascular Diagnosis and Intervention, January 27-30, 1997, pp. 83-86, for a discussion of various thrombolytic therapies including the thrombolytic brush to effect a combination of pharmocologic and mechanical lysis. Various other infusion and pulse lytic catheter therapies for accomplishing arterial and venous lysis and to preserve the patency of a thrombosed dialysis access are also described.
One of the described therapies involves "weep" infusion of the thrombolytic agent through a plurality of infusion holes in an infusion segment of a coiled catheter of the type disclosed in U.S. Pat. No. 5,554,114 to Wallace et al. or of a straight catheter having a penetrable distal "valved-tip" for allowing advancement of the catheter over a guidewire as disclosed in U.S. Pat. No. 5,085,635 to Cragg, incorporated herein by reference. In this technique, thrombolytic agent is delivered at a constant low pressure through the catheter lumen and out of the infusion holes over a prolonged period of time. This approach has been used to provide weep infusion treatment of an elongated Deep Vein Thrombosis (DVT) as also described by N. H. Patel M. D. in the publication "Deep Vein Thrombolysis", by Micro Therapeutics, Inc. As described therein, urokinase infusion at 250,000 units/hour was delivered for 30 hours followed by a reduced volume of infusion delivery for another 7 hours to dissolve an elongated DVT in a patient suffering from a number of illnesses. While treatment of this nature is quite promising, it is costly due to the time that the patient is hospitalized and the amount of thrombolytic agent that is infused. In this case, more than 7,500,000 units of urokinase was infused to treat this patient.
Reference is also made in the above-referenced Cragg article to the article by J. J. Bookstein M. D. et al. entitled "Pulse-Spray Pharmocomechanical Thrombolysis", Cardiovascular Interventional Radiology, (1992) 15:228-233. The pulse spray system is also disclosed in the "Pulse*Spray.RTM. Pulsed Infusion System" literature of E. Z. EM, Inc. (.COPYRGT. ANGIODYNAMICS.RTM. 11/94, 4 pp.) and in certain embodiments of U.S. Pat. No. 5,267,979 to Appling et al. In such pulse spray approaches, a catheter is used having a guidewire lumen extending to an open distal end allowing it to be introduced over a previously positioned guidewire to position a distal infusion pattern into a thrombus. In order to close the open distal end of the lumen, it is necessary to leave the guidewire in the lumen, which decreases the open cross-section and capacity of the catheter lumen to receive thrombolytic agent. The thrombolytic agent is injected into a side port of the proximal end assembly while the open distal end is occluded. The thrombolytic agent is ejected from the catheter lumen through a number of slits through the side wall of the catheter that are arranged in a circumfluent pattern in an infusion segment. Ejection of the thrombolytic agent through the slits is effected by manually expelling it from a 10 cc or smaller syringe and into the catheter lumen as described in the Bookstein et al. article and shown in FIG. 2 of the article. The thrombolytic agent is manually ejected at relatively low pressure and velocity from the slits. The manual injection procedure is repeated at about one or two pulses per minute intervals for about an average 20-35 minutes for lysing thrombi in dialysis grafts and about 60-120 minutes in the for lysing thrombi in a variety of vascular locations.
Attention is further directed to U.S. Pat. No. 5,370,609 to Drasler et al. disclosing a thrombectomy catheter device for axially applying one or more high pressure stream of sterile saline into a thrombus to emulsify the thrombus and propel the emulsion proximally through a catheter lumen for disposal. One of the high pressure streams is provided to establish a flow that draws the thrombus into the path of the other high pressure stream to emulsify it and then directs the fragments proximally through an evacuation lumen for disposal outside the patient's body.
A mechanical thrombus maceration catheter device is disclosed in U.S. Pat. No. 5,569,275 to Kotula et al. At least one impeller at the distal end of a drive shaft and located within a distal end housing is rotated at high speed, and the thrombus is macerated by the rotor as the distal end housing is advanced through it, and the macerated blood and thrombus fibrin particles are suctioned out of the blood vessel through a catheter lumen.
A further method of lysing thrombi employing the application of plasminogen activators in conjunction with pulsed mode ultrasound energy is disclosed in U.S. Pat. No. 5,399,158 to Laur et al.
In general, in approaches involving withdrawal of blood and fibrin particles, a great deal of blood may be withdrawn and need to be replaced, which is undesirable. Moreover, the axially directed fluid jets and the impeller maceration bores holes through thrombi, but can leave remnants behind adhering to the vessel wall or breaking free to flow away. The weep and pulse spray techniques and apparatus consume a great deal of expensive thrombolytic agent and a prolonged treatment of the patient which both add to the cost of the procedure. Despite these improvements in the art, a need remains for more rapid, efficacious, and less traumatic methods and apparatus for arterial, venous and vascular access lysis of thrombi, particularly DVTs.